Papel dos achados histopatológicos e sorológicos no diagnóstico precoce de recidiva na hanseníase e falência terapêutica

Abstract

Introduction: Leprosy is an ancient infectious granulomatous disease, and still is a public health problem worldwide. Despite advances, technological resources are not universally accessible. Treatment with multidrug therapy (MDT) has reduced leprosy prevalence, nonetheless elimination will not be achieved easily. At least not until objective criteria for real leprosy healing are defined. Besides, therapy failure (TF) and leprosy relapse (LR) are underreported problem. Objectives: We divided this research into two studies. The main objective was to detect histopathological, serological and molecular laboratory factors for relapse (Study 1) and therapy failure (Study 2) in leprosy. Materials and methods: These are case-control studies with 756 paired individuals followed up at a national reference center for leprosy. In Study 1, 40 relapse cases and 40 control cases were included. In Study 2, 40 cases of therapy failure and 40 control cases were included. Clinical, epidemiological and laboratory variables were analyzed at the end of MDT, with inference to skin histopathological findings and compared with the results of serological (anti-PGL-I) and molecular tests. Results: In study 1, in skin samples, neural/perineural lymphocytic infiltrate (OR=4.67; p=0.0076) and foamy granuloma (OR=15.55; p=0.0005) resulted in respective increased odds of 4.7 and 15.6 for LR. Furthermore, hBI ≥ 3+ resulted in sensitivity and specificity of 72% and 65%, respectively, for detecting LR (AUC: 0.72; p=0.0002). No associations were found for the other histological surrogates. Concerning serology (anti-PGL-I), the ELISA index (EI) ≥ 1 resulted in 4.7 greater odds (OR=4.67; p=0.0031) for LR. Neural/perineural lymphocytic infiltrate (OR=4.58; p=0.0350), foamy granuloma (OR=7.36; p=0.0212), and histological bacilloscopic index (hBI) ≥ 1 in the skin sample (OR=1.39; p=0.0485) and EI ≥ 1 (OR =1.19; p=0.0628) were analyzed together and showed significantly higher probability of up to 94.32% for LR. In study 2, foamy granuloma (OR=7.36; p=0.0012) hIB (OR=1.55; p=0.0004) were associated with TF, increasing odds at 7.36 and 1.55, respectively. Additionally, hIB ≥ 3+ resulted in a sensitivity and specificity of 73% and 78%, respectively, for detecting TF (AUC: 0.75; p=0.0001). No associations were found for the other histological surrogates (p > 5). EI ≥ 1 resulted in a increased odds of 1.4 (OR=1.4; p=0.0019) for TF. If IE ≥3.95, sensitivity and specificity of 79% and 59%, respectively, were found for TF (AUC: 0.74; p=0.0001). Mycobacterium leprae DNA positivity by qPCR resulted in an increased 3.43-fold (OR=3.43; p=0.0201) for TF. Neural/perineural lymphocytic infiltrate (OR=4.06; p=0.0233), foamy granuloma (OR=8.41; p=0.0002), hBI ≥1 (OR=1, 55; p=0.0030) and EI ≥1 (OR=1.26; 95%CI1.00-1.58; p=0.0030) together were capable of predicting a probability of up to 95.41% for the FT. Conclusions: Histopathological, serological and molecular findings at the end of MDT are capable of discriminating those patients with a greater chance of leprosy relapse and failure treatment. Finally, the results reinforce the importance of pathological skin examination for monitoring therapeutic response to MDT. Therefore, we propose the use of laboratory tools to objectively defining criteria for the real cure for leprosy.